Sodium hydride → HCID 73056533, compound

HRID 1052260Notes

Reaction equation

HRID 1052260 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][NH:25][CH:26]=4)[N:19](S(C4C=CC=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[H-].[Na+].CS(O[CH:43]1[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]1)(=O)=O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][C:13]2[N:14]=[C:15]3[CH:21]=[C:20]([C:22]4[CH:23]=[N:24][N:25]([CH:43]5[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]5)[CH:26]=4)[NH:19][C:16]3=[N:17][CH:18]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 41906811-Methylpiperidin-4-yl methanesulfonateHCID 89963624HCID 89963624, compound

Product 1

HCID 73056533HCID 73056533, compoundYield 4.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
55 °C

Procedure

To a stirred solution of 2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-6-(1H-pyrazol-4-yl)-5H-pyrrolo[2,3-b]pyrazine (from Example 35, Step 1, 50.0 mg, 0.102 mmol) in N,N-dimethylformamide (2.0 mL), sodium hydride (6.13 mg, 0.153 mmol) was added at 0° C. After 15 minutes, a solution of 1-methylpiperidin-4-yl methanesulfonate (23.7 mg, 0.122 mmol) in N,N-dimethylformamide (1 mL) was added. The reaction mixture was then warmed up to 55° C. After 2 hours, the reaction was quenched with water, and extracted with methylene chloride. The combined organic layers were dried over MgSO4, then filtered and concentrated. The crude mixture was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (2.2 mg) as its TFA salt. LCMS calculated for C25H31N6O2 (M+H)+: m/z=447.3. Found: 447.3.

Workup

  1. waitAfter 2 hours
  2. customthe reaction was quenched with water
  3. extractionextracted with methylene chloride
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude mixture was purified on RP-HPLC (XBridge C18 column
  8. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-0499fd991e6e4be9855d2d8b50f5dd9a
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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